Arginine based peptide micelle for siRNA delivery

Abstract

In this research, RV peptides with 1~4 arginines and 6 valines were synthesized and evaluated as carriers for intracellular delivery of plasmid or siRNA. RV peptides formed micelles in aqueous solution with cationic arginines on the surface and hydrophobic valines in the core. Gel retardation assays showed that plasmid or siRNA was completely retarded at a 5/1 weight ratio (peptide/plasmid or siRNA). To evaluate the stability of RV peptide/siRNA complex, heparin competition assays were performed. The results showed that heparin replaced siRNA in polyethylenimine (PEI)/siRNA complex at a 4/1 weight ratio (heparin/siRNA). However, RV peptide/siRNA complex was stable up to an 8/1 weight ratio (heparin/siRNA), suggesting that RV peptide/siRNA complex is more stable than PEI/siRNA complex. In transfection assays with plasmid, pCMV-Luc, R3V6 peptide had higher plasmid delivery efficiency than any other RV peptides. R3V6 peptide was more efficient than PLL. However, PEI had much higher plasmid delivery efficiency than R3V6 peptide suggesting that RV peptides are not suitable for plasmid delivery. For siRNA delivery, anti-luciferase siRNA was complexed with RV peptides and delivered into luciferase-expressing 293 cells. R3V6 peptide was more efficient than PEI and PLL in silencing luciferase gene. In addition, MTT assay showed that all RV peptides are less toxic than PEI or PLL. The results suggest that R3V6 peptide will be useful for delivery of siRNA.